9M3P
Crystal structure of human pyruvate dehydrogenase kinase isoform 1 in complex with ATP competitive inhibitor 3
Summary for 9M3P
| Entry DOI | 10.2210/pdb9m3p/pdb |
| Related | 9M3O |
| Descriptor | [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial, POTASSIUM ION, N-[4-(2-chloro-5-methylpyrimidin-4-yl)phenyl]-N-(4-{[(difluoroacetyl)amino]methyl}benzyl)-2,4-dihydroxybenzamide, ... (5 entities in total) |
| Functional Keywords | ghkl atpase/kinase family, pyruvate dehydrogenase complex, mitochondrial kinase, transferase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 45210.19 |
| Authors | |
| Primary citation | Xu, H.,Ding, D.,Han, X.,Miao, K.,Liang, C.,Yun, H.,Zhu, W.,Dey, F.,Zhao, D.,Wu, Y.,Reutlinger, M.,Yang, J.,Zhai, G.,Lin, Z.,Li, C.,Wu, W.,Xu, B.,Han, L.,Chen, S.,Huang, X.,Casagrande, F.,Hilbert, M.,Strebel, Q.,Wichert, M.,Westwood, P.,Schafer, R.,Roth, D.,Heer, D.,Tian, X.,Ma, T.,Zhang, T.,Zhao, J.,Urich, E.,Xia, G.,Lassen, K.,Shen, H.C.,Zou, G. Discovery of ATP competitive PDHK1/2 dual inhibitors. Bioorg.Med.Chem.Lett., 122:130190-130190, 2025 Cited by PubMed Abstract: Multiple screening approaches were carried out to identify novel chemistry starting for Pyruvate Dehydrogenase Kinases (PDHKs) inhibitors. Through hit triaging efforts and structure-based optimization, two series of ATP competitive inhibitors with single digit nanomolar enzymatic potency for PDHK1/2 and around 10-100-fold selectivity over PDHK4/3 were discovered. Approach of covalent inhibitor was explored to successfully improve the cellular target engagement to single digit micromolar range. PubMed: 40107630DOI: 10.1016/j.bmcl.2025.130190 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.01 Å) |
Structure validation
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